chr22-19800213-C-T

Variant names:

• chr22-19800213-C-T
• rs748806
• NM_053004.3:c.732+1788G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_053004.3(GNB1L):​c.732+1788G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,260 control chromosomes in the GnomAD database, including 1,770 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1770 hom., cov: 33)
• Consequence: GNB1L NM_053004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 15 publications found

Genes affected

GNB1L (HGNC:4397): (G protein subunit beta 1 like) This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. The gene maps to the region on chromosome 22q11, which is deleted in DiGeorge syndrome, trisomic in derivative 22 syndrome and tetrasomic in cat-eye syndrome. Therefore, this gene may contribute to the etiology of those disorders. Transcripts from this gene share exons with some transcripts from the C22orf29 gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3	c.732+1788G>A		intron_variant	Intron 7 of 7	ENST00000329517.11	NP_443730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB1L	ENST00000329517.11	c.732+1788G>A		intron_variant	Intron 7 of 7	1	NM_053004.3	ENSP00000331313.6
GNB1L	ENST00000403325.5	c.732+1788G>A		intron_variant	Intron 6 of 6	1		ENSP00000385154.1
GNB1L	ENST00000405009.5	c.630+1890G>A		intron_variant	Intron 7 of 7	1		ENSP00000384626.1
GNB1L	ENST00000460402.5	n.700+1788G>A		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18739 AN: 152142 Hom.: 1767 Cov.: 33

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18751 AN: 152260 Hom.: 1770 Cov.: 33 AF XY: 0.128 AC XY: 9563 AN XY: 74456

African (AFR) AF: 0.0548 AC: 2279 AN: 41562

American (AMR) AF: 0.222 AC: 3389 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3472

East Asian (EAS) AF: 0.477 AC: 2459 AN: 5150

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4828

European-Finnish (FIN) AF: 0.0591 AC: 628 AN: 10624

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7695 AN: 68010

Other (OTH) AF: 0.125 AC: 265 AN: 2112

Alfa AF: 0.127 Hom.: 1152

Bravo AF: 0.132

Asia WGS AF: 0.292 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.093
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs748806; hg19: chr22-19787736;